Innate and adaptive immune response in the persistence of Pseudomonas aeruginosa and mycobacterial lung infection in cystic fibrosis

• Grant number: 19/08598-9
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2019 - June 30, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Marcos Tadeu Nolasco da Silva
• Grantee: Marcos Tadeu Nolasco da Silva
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Carlos Emilio Levy ; Niels Høiby ; Renan Marrichi Mauch

Abstract

Pulmonary disease is the major cause of morbidity and mortality in patients with cystic fibrosis (CF), with Pseudomonas aeruginosa being the predominant pathogen, mainly due to the mechanisms of adaptation of this bacterium to the stress conditions of the CF airways, which includes the biofilm formation, leading to a persistent infection, accompanied by an intense, mainly IgG-mediated inflammatory response, without clearing the infection. This is possibly due to the impairment of immune memory formation against the pathogen despite repeated exposure to its antigens. Other emerging pathogens have been shown to play a significant role in the pulmonary disease, including non-tuberculous (or atypical) mycobacteria (NTM), which are commonly found in patients from European CF reference centers, particularly in Denmark. However, the prevalence of these pathogens in our center has proved to be low, even after a systematic screening, which may be a consequence of the administration of the anti-tuberculosis Bacille Calmette-Guérin (BCG) vaccine routinely applied in a single dose in neonates in Brazil. Here, we propose to set a profile of the innate and adaptive immune responses in different groups of CF patients classified according to their P. aeruginosa colonization/infection status - never colonized, free of infection, intermittent colonization and chronic infection - by means of flow cytometric phenotyping and gene expression analyses. This will help to better understand the foundations of immune failures in CF and, possibly, the mechanisms used by P. aeruginosa to evade the immune responses, and may also serve as a basis for other models of chronic infections. Such knowledge will potentially provide a support for the study of immunotherapeutic approaches as well as personalized medicine in the setting of CF chronic lung infection, aiming at functional preservation and survival improvement. We also intend to evaluate and compare the innate and adaptive immune responses against NTM between Brazilian and Danish patients and to investigate the relationship between the BCG vaccine and the low prevalence of NTM infection in our center. This project will reinforce the already established international partnership between the CF study groups of Unicamp and Copenhagen University Hospital (Rigshospitalet), University of Copenhagen, Denmark. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MAUCH, RENAN M.; ALVES, PAULO CESAR M.; LEVY, CARLOS E.; RIBEIRO, JOSE D.; RIBEIRO, ANTONIO F.; HOIBY, NIELS; NOLASCO DA SILVA, MARCOS T.. Lymphocyte responses to Mycobacterium tuberculosis and Mycobacterium bovis are similar between BCG-vaccinated patients with cystic fibrosis and healthy controls. Journal of Cystic Fibrosis, v. 19, n. 4, p. 575-579, JUL 2020. (19/08598-9, 18/10614-0)